Stem cells are regarded as a promising therapeutic candidate material for various diseases due to the multipotency thereof. For example, mesenchymal stem cells (MSCs) release many nutritional factors that can be easily obtained and isolated and achieve the promotion of angiogenesis and the inhibition of inflammation (Non-patent literature 1). These characteristics of MSCs have been considered in studies for the application to the treatment of a number of human diseases. Recent studies have found that MSCs contribute to the tissue repair in a large number of animal models and human clinical treatments (Non-patent literatures 2, 3). Several reports stated the in vitro differentiation ability of MSC into the neural lineage (Non-patent literature 4) and astrocytes (Non-patent literature 3), but there is no definite evidence as to what functions the differentiated cells perform in vivo. It seems that the favorable effect of MSCs is induced by paracrine mechanisms rather than cell replacement, and therefore, the transplantation of MSCs would have temporary and limited effects but not the alleviation maintained for a long period of time (Non-patent literature 5).
In contrast, embryonic stem cells (ESCs) can differentiate into cell types derived from all three embryonic germ layers, and have a strong self-renewal ability. Noticeably, neural precursor cells (NPCs) derived from ESCs, first, differentiate into a particular cell type of neural lineage cells including neural cells, astrocytes, and oligodendrocyte, and thus are considered to be an ideal cell source for repair or regeneration of damaged brain tissues. These cells secrete certain factors for promoting the survival and proliferation of endogenous neural precursor cells (Non-patent literature 6). However, it has not yet been known how NPCs differentiated from ESCs or the conditioned medium of NPCs contribute to the improvement of functions after administration into disease models
Reprogrammed stem cells refer to cells reprogrammed to acquire pluripotency by subjecting somatic cells to an artificial reprogramming procedure through various means, such as gene transduction/transcriptional factor induction, chemical treatment and growth factor treatment. The reprogrammed stem cells are called induced pluripotent stem cells (iPSCs) (non-patent document 7). When compared with embryonic stem cells, these cells show very high similarity in view of cell morphology, culture condition, proliferation rate, gene expression profile, chromosomal alteration patterns, pluripotency, and teratoma forming ability in immunodeficient mice. The differentiation potency of the induced pluripotent stem cells is similar to that of embryonic stem cells, but it is not well known how NPCs differentiated therefrom or an NPC conditioned medium contributes to the improvement of functions after administration into disease models.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosure of the cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and the details of the present invention are explained more clearly.